Ethers of hydroxy-beta-phenyl-azo-alpha-alpha-diamino-pyridines



Patented May 3, 1932 "UNITED STATES PATENT OFFICE EDMOND '1. TISZA AND BERNARD JOOS, OF YONKERS, NEW YORK, ASSIG-NORS TO THE PYRIDIUM CORPORATION, OF NEI'ERA. PARK, NEW YORK, A CORPORATION OF NEW YORK ETHERS F HYDROXY-BETA-IHENYL-.AZO-ALPHA-ALPHA-DIAMINO-PYRIDINES Nb Drawing; v Application filed June 16,

This invention is an improvement in ethers of hydroxy-beta-phenyl-azo alpha alphadiamino-pyridines, in the methods of preparing the same for medicinal use, and in the v utilization ofthe substances in the treatment which when administered will appear in a relatively high concentration in the urine, giving to it from an orange to deep brownish red color, thus to insure a strong action on pathogenic germs in the urinary tract.

In our application Serial No. 348,114, filed on March 18th, 1929, we have shown that the coupling of diazotized amino phenols with alpha-alpha-diamino-pyridine produces valuable medicinal susbtances, and the present invention is a carrying further of the process ofthe said, application.

The simplest ethers, the methoxyand ethoxycompounds of hydroxy-beta-phenyl azo-alpha-alpha-diamino-pyridines can be obtained in difierent ways. As for instance, by alk ylating the sodasalt solutions of hydroxybeta-phenyl-azo-alpha alpha diamino pyridine with alkyl iodine or alkyl sulphate. Or they may be obtained by coupling diazotized anisidines or phenetidines with alpha-alphadiamino-pyridine in the following manner.

Example Copulation begins at once, and the reaction 1930. Serial No. 461,626.

mixture is put aside over night. On the following morning, sodium acetate solution, (17 B.) is added until only a slightly acid reaction with congo paper is noted. The

mixture is then set aside for ten hours, when the hydrochloride of the dye-stufi is collected on a suction filter, Washed with water and dried.

The resultant compound varies, of course, with the amino-phenol ether used. With panisidine, the resultant product is p-methoxy-beta-pheny lazo-alpha alphadiamino pyridine hydrochloride, with p-phen'etidine, pethoxy betaphenyl azo alpha-alphadiamino-pyridinehydrochloride, with m-phenetidine, m-ethoxyJoeta-phenyl-azo-alphaalpha-diamino-pyridine hydrochloride, and

with o-phenetidine, o-ethoXy-beta-phenylazo-alpha-alpha-diamino pyridine hydrochloride.

The p-methoXy-beta-phenyl-azo-alpha-alpha-diamino-pyridine hydrochloride forms a dark red micro-crystalline powder. The pethoxy beta phenyl azoalphaalpha-diamino-pyridine hydrochloride forms a dark red, almost black, micro-crystalline powder.

The m-ethoxy-beta-phenyl azo-alpha-alphadiamino-pyridine hydrochloride forms a red, and the o-ethoXy-beta-phenyl-azo-alpha-alpha-diamino-pyridine hydrochloride a dark red micro-crystalline powder. All are somewhat soluble in cold water, and more so in hot water, and all are very slightly soluble in alcohol, acetone, ether, chloroform and benzol.

The bases of the several hydrochlorides may be obtained from the corresponding hydrochloride by dissolving the hydrochloride in water, and precipitating the base with alkali. Each of the bases is in the form of light yellow needles, the p-methoxy-betaphenyl azo alpha alpha diamino pyridine "hydrochloride having a melting point of 182 0., the p-ethoXy-beta-phenyl-azo-alphaalpha-diamino-pyridine hydrochloride a melting point of 178179 (1, the m-ethoxybeta-phenyl-azo alpha alpha diamino-pyridine hydrochloride a melting point of 116-.-

117 0., and the o-ethoXyJoeta-phenyl-azoalpha-alpha-diamino-pyridine hydrochloride tips.in the pyridine nucleus asthe place for and since these compounds are made through diazotization of anisidine and phenetidine and; couplingfwith alpha-alpha-diamino-pyridi ne, theformu'las fort-he compounds should be as f ollovvs:. r V

' I-P- methoxy r beta phenylazo alpha alpha-diamino-pyridine.

I II P- ethoxy -'beta -pl1enyl-azo alpha alpha' diamino-pyridine.

' -llI eM-ethoxy-beta-phenylazo al-ph'a alpha-diamino py'ridine;

' O-N UOOZHB A g mN N inn Y IVO'-ethOXy-b etaphenyl-azo alpha alpha-diami'no-pyridine, p i v, V v r 1 oozra g r V I V I v V V I g the formin we designate the beta poi the copulation. fIn general, the azo-group willfgoi'ntoipara position to the amino group or in the ortho, if the para position is occupied; In the present case, the m group is 1n para'positionto one, and In ortho posit-ion to the otherfamino group. -'The compounds Will be pg, m-',or"o-alkoXy-beta-phenyl-aZoal phaFal'pha'-diamino-pyridines. There is I a possibility that some of the gamma 'azo compound is formed and that this isomer is pres? entin the above'desoribed compounds. The statements as regards the formulas and in regard to structure are theoretical,

andare not intended as limitations. As many other alkylated hydroky beta-phenyl-azo alpha alpha-diainino-pyridinescan be made, V which are apparently widely different embodiments ofithis invention, Without departing fromthespirit thereofwe do not intend s alkylated an acid solution, and subsequently precipitatpling with alpha-alpha diamino pyridine: in

to limit ourselves to the specific embodiment herein described. 7

What is claimed as new is 1. The method of obtaining alkylated hy droxy beta-phenyl-azo-alpha-alpha-diaminopyridine hydrochlorides,-which consists in diazotizing alkoXyaminophenols and ConplingWvit-h alpha-alpha-diamino-pyridine in hydrochloric acid solution.

. 2. The methodof obtaining anfiisomer of alkylated hyd'roxy-beta-phenyl-azoalphaalpha diamino pyridine hydrochloride, WhichconsistslH dlaZOtlZlng analkoxyaminophenol andcoupling with alpha-alphadiamino pyri'dine' in hydrochloricfa'cid solu tion. 7,

3. The method of obtaininglalkylated hydroXybeta. -phenyl-aZo-alpha alphardiaminopyridine, which consists in fdiazotizing alkoxyaminoplienols and, coupling.- With alpha-alpha-diaminoepyridine an acid solution, and subsequently precipitating thefreebasewith analkalif, e w i 4. The, method of obtaining an isomer of alpha-diamino-pyridine, which consists in c diazotizing an ,alkoxyaminophenol and coil- 151m with .alpha alpha-diamino-pyridine in ing the free base withfanralkali. 3 5'...The method of obtaining an isomer of nethox'y beta phenyl-azo alpha alpha-diamino-pyridine hydrochloride, which consists in diazotizing an anisidine, and coupling With alpha-alpha-diaminmpyridine hydro-; 1 00 chloric acid solution" 6; The method or waitin a senator methoxy' beta fphenyl aizo-alpha alpha diai nino-pyridine, which coiisists in diaz otiz- 7 ing an anisidine and coupling with alpha-1 alpha diaminO-pyridi'ne inan acid solution, and subsequently precipitating the free base with an alkali. r i

. 7. The method f trimming eulogyetaphenyl azo alpha alpha-d iamindpyridi'ne hydrochloride/s, which'consists in diazotiz'ing phenetidines'and coupling with alpha-alphadiamino-pyridine in hydrochloric acid solution; v. .7 is

ethoxylbeta -phenyl afzo' alplia alpha-diamino-p'y'ridine hydrochloride, which consists in diazotizing aphenetidine and conh-ydrochloiric acid soliition;

9. Tl1e",1nethod of obt ining' ethoxy-beta- I phen-y'il azo-alpha alpha diamino-pyridines, whichc'onsists in dia'zoti'zing; phenetidines and coupling". with alpha a lpha-diaminopyridine'in an acid solution, and subsequently 1 precipitating. the free base'with an alkali. v

10.: The:method'ofobtaining a isomer bf ethogy' --beta; phenfl: alph -alpha dt a phenetidineand coupling vvith al pha-alpfiai 13o liydioxy beta-phenyl-azo-alpha- 3 8. The method offolitainin 'an isomer of1i diamino-pyridine in an acid solution, and subsequently precipitating the free base with an alkali,

11. A medicinal substance, for use in the treatment of germ infections, including an isomer of alkylated hydroxy-beta-phenyl- I azo-alpha-alpha-diamino-pyridine.

day of June, A. D. 

